Hydrogenations enantioselective

This thoroughly revised and updated new edition is a must for every synthetic organic chemist. New material has been added on homogene- ous diastereoselective hydrogenations, enantioselective oxidations, and novel chiral auxiliaries. 

The (R)-amino ketone is hydrogenated enantioselectively by a neutral complex [ (S)-(i )-BPPFOH RhCl]2 to give the (R,R)-isoproterenol analogue, a compound which has been shown to possess very potent /9-adrenoreceptor agonistic activity... 

Generally, the imine substrates are prepared from the corresponding ketone and amine and are hydrogenated as isolated (and purified) compounds. However, reductive animation where the C = N function is prepared in situ is attractive from an industrial point of view, and indeed there are some successful examples reported below [18, 19]. It is reasonably certain that most catalysts described in this chapter catalyze the addition of H2 directly to the C=N bond and not to the tautomeric enamine C = C bond, even though enamines can also be hydrogenated enantioselectively. 

Pfaltz and Leitner found that some imines are hydrogenated enantioselectively at a partial H2 pressure of 30 atm and 40 °C in scC02 (d = 0.75 g mL 1) containing a chiral phosphinodihydrooxazole-Ir complex to give optically active amines in up to 81 %... 

Key words ONIOM, hydrogenation, enantioselectivity, asymmetric catalysis, DFT, reaction mechanism, chiral phosphine, ab initio, valence bond, oxidative addition, migratory insertion, reductive elimination. 

METAL-FREE BR0NSTED ACID CATALYZED TRANSFER HYDROGENATION ENANTIOSELECTIVE SYNTHESIS OF TETRAHYDROQUINOLINES... 

Both carbonyl groups are hydrogenated enantioselectively in the first step to produce a diol. 

The silanethiyl radical (7) generated from the silane thiol, which is prepared from the silane using first CuCl2 and then LiSH, abstracts hydrogen enantioselectively from silicon in ( )-fraws-2,5-dimethyl-l-phenyl-l-silacyclopentane, to bring about kinetic resolution of the latter. Such reactions are rare (equation 17)28. 

Imine hydrogenation produces an N H bond, so the chiral amines produced by this method will necessarily have mono or disubstituted N atoms. Chiral NR-R R amines can, however, be produced by asymmetric hydrogenation, using N,N disubstituted iminium ions or enamines as substrates. Neither of these substrate classes has been studied to the same extent that imines have, but both can be hydrogenated enantioselectively. 

Imines can also be hydrogenated enantioselectively in SCCO2. Leitner s group (111) reported that a cationic iridium complex with the BARF anion... 

Scheme 15 illustrates the asymmetric hydrogenation of 3-keto phosphonates catalyzed by a BINAP-Ru complex, giving P-hydroxy phosphonates in up to 99% ee [61]. The sense of enantioface differentiation is the same as that of hydrogenation of P-keto carboxylic esters (see table of Scheme 3). The reactivity of the phosphonates is much higher than that of the carboxylic esters so that the hydrogenation proceeds even at 1 to 4 atm of hydrogen and at room temperature. A Ru complex of BDPP also shows high enantioselectivity [46b]. Chiral P-hydroxy phosphonates thus obtained are useful intermediates for the syntheses of phosphonic acid-based antibiotics as well as haptens of catalytic antibodies. Similarly, P-keto thiophosphates are hydrogenated enantioselectively with a MeO-BIPHEP-Ru catalyst [61b].

Among the effective diphosphine-Ru-diamine complexes used for catalyzing carbonyl hydrogenation enantioselectively is one member in which the phosphorus atoms are attached to a [2,2]paracyclophane unit. ... 

The carbon-carbon double bond in dehydrophenylalanine methyl ester, its hydrochloride salt, and its A -acetyl derivative has been hydrogenated enantioselectively over cinchonine-modified Pd giving a low excess of the S -enantiomer. In each case, a H-bonding interaction of the type -N- -H -N- is proposed between the amine function of the reactant and the quinuclidine-N of the modifier. On this basis, the mechanism is suggested to be analogous to that published for the hydrogenation of ap-unsaturated acids. 

Smith et al reported that the hydrogenation of 2-methylcinnamic acid and 2-methylpent-2-enoic acid on 1 % Pd-sihca catalysts modified with l-(iS)-e c/o-bomyloxytrimethylsilane in MeOH at 25°C results in chiral products with ee s of 22.5% and 11.6%. These results noted that modified Pt and Pd catalysts can hydrogenate enantioselectively systems with 1,3-conjugated bonds, but the transfer of these aspects for hydrogenation of 1,4-double bonds as in methyl acetoacetate (MAA) has definite difficulties because it needs to assume the enol form (En) to react (Scheme 5.32.). 

As noted in Chapter 14, the Curtin-Hanunett principle applies to this process, and high enantioselectivities are obtained under conditions when the two diastereomeric olefin complexes equilibrate faster than the addition of Because the relative rates for equilibration versus oxidative addition of Hj depend on the concentration of hydrogen, enantioselectivities often depend on the pressure of hydrogen. Enantioselectivities of reactions of MAC have been shown in some cases -to be higher at lower In addition,... 

Keywords Ruthenium Transfer Hydrogenation Enantioselective Borrowing Hydrogen C-C Bond Formation... 

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